Having developed an in vitro animal model system in the adult rat for the study of macromolecular (antigen and enterotoxin) transport across the small intestine and for the study of immunologic control mechanisms of this process, we intend to use a combination of morphologic, physiologic and immunologic techniques to study in vivo mechanisms (s) of intestinal antibody function under more physiologic conditions. We plan to investigate means of stimulating the local immune system by oral immunization techniques, to study conditions that result in "pathologic" uptake of macromolecules (altered digestion or mucosal integrity), to characterize clinical conditions that may be associated with enhanced antigen transport (prematurity, malnutrition) and to determine the importance of macromolecular transport in the pathogenesis of disease. The uptake of antigen, adherence of antigen to intestinal cells and breakdown of antigen by pancreatic enzymes will be studies using 125I-BSA and 125I-BGG in intraperitoneally/orally immunized rats. Attempts to enhance oral immunization with BSA and BGG will be tried using adjuvants, neutralization of gastric acidity, pancreatic duct ligation and polycharged cations to alter intestinal surface charge. These procedures may either increase the "antigen mass" presented to intestinal lymphoid tissue or enhance the responsiveness of this tissue to antigens. The mechanism of tolerance and its association with the processing of oral antigens by the intestine will also be studied. Finally, the uptake of BSA, BGG, or egg albumin in premature infants, newborns and in a variety of gastrointestinal disease states will be measured by radioimmunoassays. Human biopsy material and intestinal microvillous membrane separation techniques will be used to determine the associations of antigen/enterotoxin uptake with pathologic mechanism of gastrointestinal allergy and enterotoxin diarrhea. The results of these studies may provide a basis for understanding the role of an altered gastrointestinal barrier to macromolecules in the pathogenesis of intestinal and systemic diseases.